Ampholytic Peptides Consisting of an Alternating Lysine/Glutamic Acid Sequence for the Simultaneous Formation of Polyion Complex Vesicles

Nanoarchitectures such as micelles and vesicles that self-assemble via electrostatic interactions between their charged polymeric components have been widely used as material delivery platforms. In this work, ampholytic peptides with a sequence of alternating lysine and glutamic acid residues were designed and synthesized via chemoenzymatic polymerization. This alternating sequence was achieved by trypsin-catalyzed polymerization of a dipeptide monomer. Due to the electrostatic interaction between the anionic and cationic residues, the prepared ampholytic peptides spontaneously formed nanosized assemblies with a size of 100-200 nm in water. Modification with tetra(ethylene glycol) (TEG) at the